No abstract

The role of mitochondria in amyloid βpeptide (Aβ)‐induced cytotoxicity is unclear. We therefore exposed NT2 cells, a clonal human teratocarcinoma cell line capable of differentiation into terminal neurons, to Aβ 25–35 or to Aβ 1–42 to evaluate cell viability and altered mitochondrial function. A 24‐h incubation of native NT2 cells (ρ+ cells) with Aβ 25–35 or with Aβ 1–42 produced a dose‐dependent decline in MTT reduction. Aβ 1–42 was shown to be more toxic compared with Aβ 25–35. Aβ 25–35 toxicity was prevented or diminished by a 22‐h preincubation with antioxidants (vitamin E, melatonin, and idebenone), as well as by simultaneous incubation with GSH or the nicotinic receptor agonist nicotine. Aβ 25–35 exposure was also associated with (1) inhibition of mitochondrial respiratory chain complexes (I, NADH‐ubiquinone oxidoreductase; II/III, succinate‐cytochrome c oxidoreductase; and IV, cytochrome c oxidase), (2) ATP depletion, and (3) reduction of the mitochondrial membrane potential. In contrast, NT2 cells rendered incapable of oxidative phosphorylation via depletion of their mitochondrial DNA (ρ0 cells) were unaffected by exposure to Aβ 25–35 or Aβ 1–42. These data indicate that Aβ can disrupt mitochondrial function and that such disruption causes oxidative stress. It is further suggested that a functional mitochondrial respiratory chain is required for Aβ toxicity.

Objectives: Peroral cholangioscopy (POC) has shown to be a useful diagnostic procedure in the evaluation of biliary strictures; however, data regarding its role on preoperative staging are scarce. The aim of this study was to evaluate POC role in the diagnosis and preoperative intraductal staging of perihilar cholangiocarcinoma (CCA). Methods: Retrospective study that included all patients who underwent POC with SpyGlass TM Direct Visualization System for the diagnosis of biliary strictures or for preoperative evaluation of extrahepatic biliary tumors, between 2015 and 2019, in a single tertiary center. Results: Forty-three patients were included, 63% male with a median age of 62 years. Thirty-eight (88.3%) underwent POC due to indeterminate biliary strictures, 3 (7%) due to bile duct filling defect, and 2 (4.7%) for intraductal staging of perihilar CCA. In the follow-up, a final diagnosis of malignancy was established in 56% of the patients. Visual impression accuracy with SpyGlass was 95.1% (with 100% sensitivity and 89.5% specificity). SpyBite biopsies accuracy was 80.5% (63.6% sensitivity and 100% specificity). In the 19 patients with a final perihilar CCA diagnosis, intraductal evaluation with SpyGlass altered anatomic classification (Bismuth-Corlette) defined by previous imagiologic findings in 8 (42.1%) patients. Alteration in anatomic classification changed therapeutic approach in 4 (21%). Conclusions: POC use for evaluating intraductal spread in potentially resectable perihilar CCA can detect more extensive and change surgical management. In the future, preoperative staging of perihilar CCA with POC combined with imagiologic evaluation of vascular extension of the lesions may optimize surgical results.

No abstract